Interestingly, the global hypomethylation of DNA and histones has been shown to progressively increase in parallel with advanced grade and disease progression in human cancers (Kim et al, 1994; Qu et al, 1999; Soares et al, 1999; Piyathilake et al, 2001).
Indeed, H3.3 has been shown to progressively replace most H3.1/2 in terminally differentiated cells in vertebrates.
Persistent antigenic stimulation has been shown to progressively and irreversibly down-regulate CD28 expression on CD8+ T cells [ 12].
The early process of osteoarthritis has been shown to progressively change the microstructure of trabecular bone in the tibia, with increased trabecular thickness and density but reduced mechanical properties of the subchondral cancellous bone (Ding et al. 2003).
Moreover, the dose-response curve has been shown to shift progressively to the left in patients receiving iNO continuously for several days [20], implying that the optimal dose of iNO must be determined by titration against the therapeutic target in each patient at least each day.
Likewise, antibody repertoire has been shown to be progressively shaped by changes in microbiota and to adjust to the latest microorganisms present [ 145].
In accordance with a continuum model of psychosis [ 40] the rate that individuals from the normal population report hearing hallucinations in random noise has been shown to be progressively greater across groups with increasing familial risk for psychosis [ 21].
Protein degradation in this model has been shown to increase progressively with increasing weight loss between 15 and 30%, up to a maximum increase of 240% at a weight loss of 30% (Smith and Tisdale, 1993a).
Moreover, the dose-response curve has been shown to shift progressively to the left in patients receiving iNO continuously for several days [ 20], implying that the optimal dose of iNO must be determined by titration against the therapeutic target in each patient at least each day.
2, 3 Selenium has been shown to be depleted progressively with the stages of HIV infection, 2, 3 and correlate with low CD4+ cell count and disease progression.
